Toxoplasma Gondii

TOXOPLASMA GONDII

The term coccidia describes a group of protozoa that contains the genus Cryptosporidium (see intestinal parasites) as well as a number of important veterinary parasites . Toxoplasma gondii is an intestinal coccidian but the major pathology of infection is associated with other tissues and organs. T. gondii infects members of the cat family as definitive hosts and has a wide range of intermediate hosts. Infection is common in many warmblooded animals, including humans. In most cases infection is asymptomatic, but devastating disease can occur congenitally in children as a result of infection during pregnancy. T. gondii infection in humans is a worldwide problem, although the rates of human infection vary from country to country. The reasons for these variations include environmental factors, cultural habits and the presence of domestic and native animal species. The frequency of postnatal toxoplasmosis acquired by eating raw meat and by ingesting food contaminated by oocysts from cat faeces (oocyst formation is greatest in the domestic cat) is not well established but is thought to be significant. Widespread natural infection is possible because infected animals may excrete millions of resistant oocysts, which can survive in the environment for prolonged periods (months–years). Mature oocysts are approximately 12 μm in diameter and contain eight infective sporozoites.

T. gondii infection in most animals including humans is asymptomatic. Severe disease in humans is observed only in congenitally infected children and in immuno-suppressed individuals. The most common symptom associated with postnatal infection in humans is lymphadenitis which may be accompanied by fever, malaise, fatigue, muscle pains, sore throat and headache (flulike symptoms). Typically infection resolves spontaneously in weeks or months, but in immuno-suppressed individuals, a fatal encephalitis may occur producing symptoms such as headache, disorientation, drowsiness, hemiparesis, reflex changes and convulsions. Prenatal T. gondii infections often target the brain and retina and can cause a wide spectrum of clinical disease. Mild disease may consist of impaired vision, whereas severely diseased children may exhibit a ‘classic tetrad’ of signs: retinochoroiditis, hydrocephalus, convulsions and intracerebral calcifications. Hydrocephalus is the least common but most dramatic lesion of congenital toxoplasmosis.

The life cycle of T. gondii was only fully described in the early 1970s when felines including domestic cats were identified as the definitive host and various warmblooded animals were identified as intermediate hosts. T. gondii is transmitted by three mechanisms: congenitally, through the consumption of uncooked infected meat and via faecal matter contamination. Figure 6.5 shows the life cycle of T. gondii. Cats acquire Toxoplasma by ingesting any of three infectious stages of the organism: the rapidly multiplying forms, tachyzoites, the dormant bradyzoites (cysts) in infected tissue and the oocysts shed in faeces. The probability of infection and the time between infection and the shedding of oocysts varies with the stage of T. gondii ingested. Fewer than 50% of cats shed oocysts after ingesting tachyzoites or oocysts, whereas nearly all cats shed oocysts after ingesting bradyzoites. When a cat ingests tissue cysts, the cyst wall is dissolved by intestinal and gut proteolytic enzymes, which causes the release of bradyzoites. These enter the epithelial cells of the small intestine and initiate the formation of numerous asexual generations before the sexual cycle begins. At the same time that some bradyzoites invade the surface epithelia, other bradyzoites penetrate the lamina propria and begin to multiply as tachyzoites (trophozoites) (Figure 6.2c). Within a few hours, tachyzoites may disseminate to other tissues through the lymph and blood. Tachyzoites can enter almost any type of host cell and multiply until the cell becomes packed with parasites. The host cell then lyses and releases more tachyzoites to enter new host cells. The host usually controls this phase of infection, and as a result the parasite enters the ‘resting’ stage in which bradyzoites are isolated in tissue cysts. Tissue cysts are formed most commonly in the brain, liver and muscles. These cysts usually cause no host reaction and may remain dormant for the life of the host. In intermediate hosts, such as humans, the extraintestinal cycle of T. gondii is similar to the cycle in cats except that there is no sexual stage.

Most cases of toxoplasmosis in humans are probably acquired by the ingestion of either tissue cysts in infected meat or oocysts in food contaminated with cat faeces. Bradyzoites from the tissue cysts or sporozoites released from oocysts invade intestinal epithelia and multiply. T. gondii may spread both locally to mesenteric lymph nodes and to distant organs by invading the lymphatic and blood systems. Focal areas of necrosis (caused by localized cell lysis) may develop in many organs. The extent of the disease is usually determined by the extent of injury to infected organs, especially to vital and vulnerable organs such as the eye, heart and adrenals.

Opportunist toxoplasmosis in immuno-suppressed patients usually represents reactivation of chronic infection. The predominant lesion of toxoplasmosis— encephalitis in these patients—is necrosis, which often results in multiple abscesses, some as large as a tennis ball.